2. Academic Validation
  3. m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming

m5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming

  • Cell Death Dis. 2023 Aug 15;14(8):520. doi: 10.1038/s41419-023-06049-8.
Lang Fang # 1,  Hongxin Huang # 1,  Jialun Lv # 1,  Zetian Chen # 1,  Chen Lu 1,  Tianlu Jiang 1,  Penghui Xu 1,  Ying Li 1,  Sen Wang 1,  Bowen Li 1,  Zheng Li 1,  Weizhi Wang 2,  Zekuan Xu 3 4
Affiliations

Affiliations

  • 1 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • 2 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. wwzhouse@126.com.
  • 3 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. xuzekuan@njmu.edu.cn.
  • 4 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 210029, Nanjing, Jiangsu Province, China. xuzekuan@njmu.edu.cn.
  • # Contributed equally.
PMID: 37582794 DOI: 10.1038/s41419-023-06049-8
Abstract

Abnormal 5-methylcytosine (m5C) methylation has been proved to be closely related to gastric carcinogenesis, progression, and prognosis. Dysregulated long noncoding RNAs (lncRNAs) participate in a variety of biological processes in Cancer. However, to date, m5C-methylated lncRNAs are rarely researched in gastric Cancer (GC). Here, we found that RNA cytosine-C(5)-methyltransferase (NSUN2) was upregulated in GC and high NSUN2 expression was associated with poor prognosis. NR_033928 was identified as an NSUN2-methylated and upregulated lncRNA in GC. Functionally, NR_033928 upregulated the expression of Glutaminase (GLS) by interacting with IGF2BP3/HuR complex to promote GLS mRNA stability. Increased glutamine metabolite, α-KG, upregulated NR_033928 expression by enhancing its promoter 5-hydroxymethylcytosine (hm5C) demethylation. In conclusion, our results revealed that NSUN2-methylated NR_033928 promoted GC progression and might be a potential prognostic and therapeutic target for GC.

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